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2007 Grant - Zhu

Role of DLP1 in Mitochondrial Dysfunction in Alzheimer's Disease

Xiongwei Zhu, Ph.D.
Case Western Reserve University
Cleveland, Ohio

2007 Investigator-Initiated Research Grant

Mitochondria are tiny structures within every cell that provide energy for the cell's function. Studies have suggested that mitochondria function abnormally in brain cells affected by Alzheimer's disease, and that abnormal mitochon-drial function may be partly responsible for Alzheimer pathology.

Mitochondria are continually renewed, remodeled and redistributed to meet the constantly changing needs of the cell. Some of this remodeling is controlled by a protein known as dynamin-like protein-1 (DLP1). Xiongwei Zhu, Ph.D., and colleagues have observed that levels of DLP1 are reduced in brain tissue from persons who died of Alzheimer's disease and in mice that exhibit features of the disease. They have also found evidence that mitochon-dria in cells from people with Alzheimer's disease have abnormal shapes and distributions within the cell.

Dr. Zhu and colleagues plan to continue their studies of DLP1 and its role in mitochondrial function. In particular they hope to determine how alterations in DLP1 levels may account for some of the pathological changes that occur in the brains of persons with Alzheimer's disease. They plan to examine DLP1-deficient cells using a time-lapse microscope technology that will enable them to observe changes over time in mitochondria function and general cellular function. These studies may provide important insight into one of the fundamental biochemical changes that occurs during the development of Alzheimer's disease.